Thursday, June 25, 2009

LCT has (finally) gotten government approval to start a phase-I human trial of their DiabeCell product. This is an encapsulated pig pancreas treatment for type-1 diabetes. The New Zealand government has promised this approval months ago, after years of dragging their feet, and now has finally made good on it's commitment. However one important limitation has been put on the trial: only so-called "brittle" type-1 diabetics can be enrolled.

Although LCT is downplaying the importance of this limitation, it has the potential to delay the end of the trial still further. Previously, almost any type-1 diabetic could take part in the trial, so it was easy to find patients to participate. But now, only "brittle" type-1s can participate and that will doubtless cause delays in recruiting participants. "Brittle" diabetics are those diabetics who's BG can drop very quickly. These are the guys who can pass out while driving, or regularly end up in the hospital after collapsing.

Limiting the study to brittle diabetics should make for better results, because these guys have the worst control, and therefore should see the biggest improvements. So from that point of view, it is a good thing. However, it will also slow the trial and delay completion, which is not good.

I view limiting the study to brittle diabetics as 100% political ass-covering (please excuse the language). I think the New Zealand minister of health had delayed so long, that he simply could not just say "yes", because he could have (and should have) done that months ago. So by forcing a change -- any change -- he can claim that the delay was for a good reason. But it's a pointless restriction, and totally unjustified. Pancreatic transplants, which have huge side effects are limited to brittle diabetics, but these encapsulated transplants have basically no side effects, when compared with whole organ transplants. Putting the same restrictions on the patients for one as for the other is really a farce.

LCT has previously started a phase-I human trial in Russia, and so far, 7 people have been treated as part of that study. Some have been treated more than once, and data has been publicized. Some patients in that study were insulin free for a period of a few weeks. I felt the overall results suggested that the treatment did work, but that the implants stopped working just a few months after they were implanted. Others were a lot more excited about these results than I was.

I can not find a USA Clinical Trial record for this work (probably because it is being done in New Zealand), and the information I've read in the press about the experiment make it sound like a repeat of the Russian human trial. Eight patients, for example. Hopefully they will at least use larger doses, so they can learn something new that way.

While getting permission to run this trial is a step forward, I'm not exactly sure how it leads to general availability of the treatment. It is the second phase-I study started, but no phase-II study is planned (that I know of). In the past LCT had talked about a phase-II study in Denver, but when the economy got into trouble a few months ago, they stopped talking about that, and laid off at least one of the key people involved in it. So overall, I'm happy to see them do another study, but I'm also waiting for some information on how they plan to get from phase-I trials (which they have done and are doing) to general availability of the treatment.

Tuesday, June 23, 2009

You might have seen this recently headline from Reuters:Andromeda says Teva to market diabetes treatment

This headline is quite misleading. What has actually happened is this: "Teva had decided to exercise its option to complete a $13.5 million investment to market Andromeda's treatment for Type I diabetes." This is an announcement about money, not about the availability of a treatment for type-1 diabetes.

Andromeda's treatment, called DiaPep 277 is a a "heat shock protein". This is a protein that is generated naturally by the body when stressed, and is known to help modulate immune response. The following article:
http://www.diabetesincontrol.com/results.php?storyarticle=793
contains a good overview of heat shock proteins, and how DiaPep 277 is supposed to work. But remember that the clinical trial discussed there are 7 years old at this point.

It is in the middle of a 5 year phase-III human trial, starting in June 2005 and ending in June 2011. I believe it was the earliest possible type-1 cure to go into phase-III human trials (the last phase before marketing approval). The early results were not very promising, but they added more people to the trial, and changed the way they analyzed the data, and are hoping for good results. So far, I have not seen any good news type results from this study, but Andromeda seems very positive, and Teva has put in over US$ 15 million over the last year, so they think that something is there. I just do not see it myself.

Saturday, June 20, 2009

Two pieces of news from MacroGenics:First, their phase-II human trial of teplizumab (called PROTEGE) is fully enrolled.Second, they are starting a follow on phase-III study called PROTEGE ENCORE.

Teplizumab is a "humanized monoclonal antibody" which targets the CD3 part of the immune system in order to lower (or stop) the body's autoimmune response. This drug tries to prevent type-1, or lessen it's severity, by "turning down" the immune system's attack on the body's own pancreas cells. This basic approach has resulted in treatments (but not cures) for other autoimmune diseases. It does carry the risk that the body's immune system will not properly attack a real threat.

Fully enrolling a study (especially one this large: 530 people) is important because the major reason that studies are delayed, is trouble enrolling people in them. Especially a study like this where only "honeymoon" diabetics can participate, getting 530 often takes longer than planned. But once it is fully enrolled, that source of delay is removed.

The new study is a sign that MacroGenics is looking to productize this drug. The new study is focused on "clinical responses". That's research-speak to mean "does it help patients" or "do real people benefit in a useful way from this treatment". This is the kind of trial you do just prior to putting it on the market. The new study is 400 people and is scheduled from June 2009 to June 2012.

There is also a third PROTEGE trial which is ongoing, called PROTEGE Extension, which follows patients from the PROTEGE trial for an extended length of time.

If you view the path to a cure as a race, then with this announcement MacroGenics has pulled even with ToleRx which also has a CD3 targeted humanized monoclonal antibody in phase-III human trials. (That's the DEFEND trial of Otelixizumab.) It is interesting, to me at least, to see the dance of small companies and big companies. The PROTEGE trial is sponsored by MacroGenics. The PROTEGE Extended trial by MacroGenics / Eli Lilly, and the PROTEGE Encore trial by Eli Lilly, so you can see how Eli Lilly taking over the Teplizumab treatment from MacroGenics. Similarly, ToleRx has a partnership with GlaxoSmithKline for their Otelixizumab treatment.

(Note: MacroGenics/Eli Lilly calls PROTEGE a "phase-II/III trial", and the Encore trial a phase-III. But I considered PROTEGE a phase-II and Encore a phase-III.)

You can read more about it here:http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#MacroGenics(although I really need to update this)

The web page home of this trial is here:http://www.protegediabetes.org/

Here are the US Clinical Trial entries for all three studies:http://www.clinicaltrials.gov/ct2/show/NCT00385697 (Protege)http://www.clinicaltrials.gov/ct2/show/NCT00870818 (Extension)http://www.clinicaltrials.gov/ct2/show/NCT00920582 (Encore)

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This blog discusses cures and preventatives for type-1 diabetes that are either in human trials or just about to start. Treatments for diabetes are not generally discussed here, unless they can turn into a cure or a preventative. My definition of a cure is this:1. Blood sugar control without testing and with doctor's visits 4 times a year, or less. Any cure must result in an average lifespan close to normal.2. Does not require a lifetime of immunsuppressive drugs, so it is not trading one treatment for another. (but a couple of operations, or a short course of drugs is OK)Obviously, this is my personal definition of a cure; yours may differ.Because a cure for type-1 diabetes is likely to involve a combination of several different drugs or treatments, I try to follow research into anything which may be an important part of the cure.

My Non-Conflict of Interest Statement

I don't work for a company involved in medical research; I never have.

I don't get paid in any way by any company doing medical research; I never have. And that includes free samples, free travel, or free anything.

None of the hours that I have put into my blog, or the posts that I make to any web site, has ever been paid for, nor have I gotten anything free. (Except for some very nice and heart felt thank-you emails, and those are worth more than money.)

My daughter has type-1 diabetes and participates in clinical trials. I sometimes report on trials that she participates in.